A novel variant of KCNQ1 gene and pathogenicity prediction in a family with long QT syndrome type 1

We report a novel heterozygous missense variant of KCNQ1 in a family exhibiting LQTS with complete penetrance and predict its pathogenicity through multiple prediction software programs and 3D model analysis. Whole-exome sequencing (WES) was performed in a family with symptoms of LQTS. The pathogenicity of the identified variant was predicted for its effect on a 3D model of KCNQ1, and in-depth functional analysis was performed for mechanistic speculation. A novel heterozygous variation c.716T>G in KCNQ1 with autosomal dominant inheritance was identified. We demonstrated that this variant, which is located in the conserved hot spot domain, was evaluated as likely pathogenic. In silico prediction indicated that the variation was involved in the process of channel closing/opening. This study reports a novel variation in KCNQ1 , provides supportive evidence for pathogenicity prediction and enhances variant interpretation for patients with LQTS.